PDIA3/ERp57 promotes a matrix-rich secretome that stimulates fibroblast adhesion through CCN2.

ABSTRACT: The matricellular glycoprotein thrombospondin-1 (TSP1) has complex roles in the extracellular matrix (ECM) and at cell surfaces, but relatively little is known about its intracellular associations prior to secretion. To search for novel intracellular interactions of TSP1 in situ, we carried out a biotin ligase-based TSP1 interactome screen and identified protein disulfide isomerase A3 (PDIA3/ERp57) as a novel candidate binding protein. In validation, TSP1 and PDIA3 were established to bind in vitro and to colocalize in the endoplasmic reticulum of human dermal fibroblasts (HDF). Loss of PDIA3 function, either by pharmacological inhibition in HDF or in Pdia3^-/- mouse embryo fibroblasts (Pdia3^-/- MEFs), led to alterations in the composition of cell-derived

SUBMITTER: Hellewell AL 

PROVIDER: S-EPMC8977143 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature